Metal ion chelating compounds con



Reissued Jan. 12, 1954 SISTING OF MONOPHENYL POLYALKYL- ENE POLYAMINO POLYCABBOXYLIC' ACIDS AND SALTS Frederick C. Bersworth, Verona, N. I.

No Drawing.

Original No. 2,624,756, dated January 6, 1953, Serial No. 193,541, November 1, 1950. Application for reissue August 17, 1953,

Serial No. 374,836

6 Claims.

Matter enclosed in heavy brackets appears in the original patent but forms no part of reissue specification; matter printed in italics indicates the additions made by reissue.

This invention relates to clielating compounds for metal ions in aqueous solution and has for its object the provision of a chelating compound consisting of a mono phenyl poly alkylene polyamino polycarboxylic acid or salt thereof.

Another object is to provide a germicidally active metal ion chelating compound or agent for use in aqueous solutions having a wide range in pH values.

Still another object is to provide a germicidally active metal ion chelating compound or agent for use in alkaline pH solutions.

Other objects will be apparent as the invention is more fully hereinafter disclosed.

In accordance with these objects I have discovered that when one of the amino hydrogens of an alkylene polyamine'is displaced by a phenyl group and the remaining hydrogens are displaced by acetic acid or its equivalent carboxylic groups, the resultant phenyl substituted alkylene polyamine polyacetic acid is water soluble and is a good chelating compound or agent for metal ions in aqueous solutions having an acid, alkaline and neutral pH is particularly eilective as a chelating compound or agent in alkalineiand neutral pH solutions towards alkaline earth metals and magnesium ions. In addition to being a chelating agent for metal ions over a wide pH range the halogenated mono phenyl polyacetic acid is an excellent bactericidal and fungicidal agent when both hydroxyl and halogen are present in the phenyl radical.

These propertiesgive a wide field of utility for the compound in all types 01' acid, neutral and alkaline pH solutions containing detergents and acid and alkali soap compounds, as one skilled in the art will recognize. The aromatic or phenyl groups add compatibility of this chelating amino acid to solid soap compounds, 1. e., bar soap.

The compounds of the present invention fall under the generic structural formula:

XX'A

A xQu r-dr imep-ir groups but only two of the A groups function as chelate-Iormin groups, one oi which is that on the terminal amino nitrogen remote from the nitrogen to which is attached the phenyl substituent group and the other on the next adjacent interiorly spacedamino nitrogen. This leaves the remaining A groups to function as solubilizing groups for the compound in acid and alkali pH solutions.

In general, with increase in n from 1 to 5 the chelate-iorming properties increase as well as the solubilitles oi the compound and the salts and chelates of the compound. However, as the compounds derived from ethylene diamine are the easiest to prepare and the easiest to define structurally these will be described by way oi. example but not by way of limitation, as one skilled in the art will perceive.

In the preparation 01' this series of compounds several alternative Practices are available. As

one example the production of the mono-substituted [p-nitro-chlorobenzyl ethylene diamine triacetic] p nitrophenylethvlenediaminetriacetic acid (sodium salt) will be described.

Example I One mole of p-nltrochlorobenzene is added to a large excess of ethylene diamine and is heated under pressure in sealed containers to a temperature of about 120-140 C. for an extended period oi. time for 7 to 10 hours. The amount of excess ethylene diamine is from 2 to 4 moles. The reaction solution is then placed under a reflux condenser and heated to'its refluxing temperature and caustic alkali solution is added in an amount required to neutralize the halide acid I present in the reaction solution to slight excess.

The excess ethylene diamine is then distilled oil together with some water and the precipitated sodium chloride is filtered from the hot liquids remaining. The nitro benzene derivative of the ethylene diamine forms an insoluble upper layer on cooling slightly and can be separated from the aqueous solution remaining. This insoluble layer is extracted with ultra-benzene in which the disubstituted ethylene diamine compound is soluble and the mono-substituted compound is insoluble.

The insoluble mono-substituted compound is then suspended in water in which it is slightly soluble and is carbon-methylated by the chloracetic process using 3 moles of'chloracetic acid sodium salt per mole of mono-substituted coinpound and the carboxymethylated amino acid is recovered from the reaction solution by aciditying the solution with HCl to a pH 01 about 2 at a which the mono-substituted ethylene diamine tri-aoetle acid precipitates. The mono-substituted compound also may be carboxymethylated in accordance with the process of my prior Patents Nos. 2,387,735, 2,407,645 and 2,461,519, by

appropriate additions of sodium cyanide and formaldehyde, 1. e., one molar weight of each. for

a each amino hydrogen to be replaced, whilemaintaining a' reaction temperature of about 95-l00 C. and while vigorously agitating the solution and excluding atmospheric gases from the solution by maintaining a low positive pressure of gaseous ammonia over the surface of the solution.

After the carboxymethylation reaction has been completed the reaction mixture is heated gradually to l-1l0 C. and freed of any contained ammonia. such as by passing steam there- Ha-COOH Hs-COOH Each of the acetic acid groups are chemically reactive with any basic metal compound to form a metal salt and each said group functions as a solubilizing group in the compound. Two of the acetic acid groups, one on each amino nitrogen, function as chelate-forming groups, the chelate compoimd of a divalent metal such as copper beingithe easiest to illustrate structurally:

OIN

cal-005m.

NECK-CH: I imfyci". in. v In this chelate compound the acetic acid salt group remain free to function as a solubilizing group in acid and alkaline pH- solutions. In

, alkaline pH solutions Me represents an alkali metal, ammonium or an amine. Inacid pH solutions Me is normally displaced by an acid hydrogen ion. The chelate compound of'most divalent metals is most stable in. alkaline DH solutlons and is least stable in solutions.

The [nitrobenzene] nitrophenyl group is a highly reactive group and may be separately reacted in a number of different ways to produce a plurality of chemically useful compounds.

For example, the N0: group on the aromatic nucleus may be reduced to an amino group, which may then be diazotized, and converted to a halogen by means of the Sandmeyer reaction. Also, the dlazonium salt may be hydrolyzed to a phenolic group by well-known methods.

The amino hydrogens of the phenyl amino group maybe substituted by various functional groups, such as acetic acid groups (by carboxy- 4 methylation as above described to further modify the properties of the compound.

The aromatic group may also be further modi- Bed by substitution on the aromatic ring by known reactions to give derivatives thereof which are valuable chelating agents.

The aromatic nucleus also may be readily further chlorinated to introduce at least two more chlorine atoms therein. These chlorophenyl triacetic acid ethylene diamine compounds are generally insoluble in acid aqueous solutions through, and after cooling to room temperature the poivamino acid may be obtained by neutralizsame. The main product after carboxymethylastrongly acid pH having a pH of 1.5 to 2 and may be precipitated therefrom as the free acid. The various alkali metal, ammonium and amine salts of these chlorophenyl triacetic acid ethylene diamine compounds, however, are quite soluble, in water and form chelate compounds with most divalent metal ions, particularlythe alkaline earth metal I and magnesium ions, which are stabl in alkaline pH solutions.

In place of chlorine I may us bromine and/or iodine to form the respective halo analogues of the chlorine derivative above described.

Example II a In place of p-nitrochlorobenzene as the starting material of Example I. I have found that p-chlorotoluene may be employed. The original substitution reaction with ethylene diamine requires a higher temperature C. under pressure) and a longer reaction time (10 hours), but the preparation is otherwise substantiall the tion has the formula:

Bacall-CECE? HLOOOH (1H1 COOH cn coon ortho to the amino groups. For example, with chlorine ,the following compounds is believed to be formed:

cmcoon N-G Hl-C H:-

Example In The compound 2,4,6 trichloroaniline ethylene diamine triacetic acid may be prepared by heating one mole of 2,4,6 trichloroaniline with one mole of chloroethylamine diacetic acid (clcm-cm-mcm-coonm in boiling aqueous alcohol under a refluxing condenser buflered to a neutral pH for an extended time interval with good agitation. After adjusting the pH of the'solution to a pH of 10 to 10.5 with caustic alkali one mole of chloroacetic acid sodium salt is added to the solution and the soluaction solution maybe crystallized by slow evaporation of the reaction mixture to remove the water of solution to a concentration of 40% to 50% and allowing the salt to crystallize. Alternatively, the salt may be converted to the free In place of ethylene diamine in Example I, propylene diamine may be employed in equivalent molar amount to form by the same procedure the p.-chlorophenyl propylene diamine triacetic acid compound and salt.

Example V In place of ethylene diamine in Example I. diethylene triamine may be employed in equivalent molar amounts to form by the same procedure the p-chlorophenyl' diethylene triamine tetraacetic acid. In this example four molar equivalents each of sodium cyanide and formaldehyde are required in the carboxymethylation step.

This compound has greater solubility than the triacetic acid compounds due to the fourth carboxylic acid group and does not precipitate readily as the free acid on acidification to the precipitating pH of 2.0. It may also be converted to the acid by means of a weak cation resin (carwherein alkylene is one of the group consisting of boxylic acid type) and evaporating the solution slowly and filtering crystals as formed.

In the several examples given above, it is believed apparent to anyone skilled in the art that I may substitute any aliphatic alkylene polyamine for ethylene diamine without departure from the invention to form an analogous series of compounds and that, likewise I may substitute any other phenyl compound for phenyl compounds of the specific examplw without departure from the invention-to form an analogous series of compounds with ethylene diamine or any alkylene polyamine substituted therefor. In view thereof, the examples given are believed adequate for one skilled in the art to practice the invention in the production of these analogous compounds.

Likewise, it is believed apparent that the acetic acid substituent groups may be displaced in partor in whole by an analogue acid such as propionic acid without departure from the invention and that the term "alkylene as it is employed in the generic description of the invention may be either to the formula:

-CH(CH:) -CH:-

n is a member of the group consisting of 1 to 5; A is one of the group consisting of CHz-COOH and CHa-CHz-COOH and their alkali metal, ammonium and amine salts; and X is one of the group consisting of hydrogen, hydroxyl, halogen, alkyl and alkoxyl with from one to three of the X groups being halogen.

2. The compound represented by the formula:

om-ooon ClOll-CIIfCHr-N\ 111-00011 ore-coon 3. The compound represented by the formula:

CHrCOOH N-CHrCHr-N HrCOOH CHrCOOH 4. The compound represented by the formula:

CHrCOOH CHz-OOOH CHa-COOH 6. The compound represented by the formula:

CHrCOOH orb-coon o1 CHa-CHN In cmcoon I FREDERICK C. BER-SWORTH.

References Cited in the flle of this patent or the original patent UNITED STATES PATENTS -Number Name Date 868,294 Schmidlin Oct. 5, 1907 2,195,974 Reppe et al. Apr. 2, 1940 2,489,363 Bersworth Nov. 29, 1949 FOREIGN PATENTS I Number Country Date 18,095 Great Britain of 1913 642,244 Germany Mar. 6, 1987 OTHERREFERENCES Alphen: Chem. Abs., vol. 88. col. 4943 (1944). Bischoif: Beilstein (Handbuch, 4th ed.), v 12. page 547 (1929). 

